Kynurenine Pathway Project

Lead PI: Dr Seray Adams, Macquarie University, NSW

Research idea

Brain cancer patients have impaired immune system function which promotes cancer growth. One metabolic pathway which impairs the immune system in brain cancer patients is the kynurenine pathway and our research strategy for treating brain cancer patients is to investigate novel therapeutics that target the kynurenine pathway to restore normal immune system function to halt brain cancer growth.

Problem

The involvement of the lower segment of the kynurenine pathway in brain cancer pathophysiology and immunosuppression remains unexplored. Studying how brain cancer cells may exploit the lower segment of this pathway may lead to novel therapeutic strategies. An immediate need in oncology is biomarkers. Our research aims to identify several blood kynurenine pathway metabolites as biomarkers, which can be used for diagnosis and prognosis.

Why now?

The kynurenine pathway has received a considerable amount of attention during the past decade for its involvement in mediating cancer immune suppression. Our previous research has made rapid advances in understanding how brain cancer cells hijack the kynurenine pathway for their survival and growth. Therefore, our current research aims to build on our exciting preliminary data.

Approach

Targeting the lower segment of the kynurenine pathway will be a unique approach, as the majority of current research focuses on the higher segment of the pathway. Further, the whole kynurenine pathway metabolite profile can be easily ascertained by a simple and inexpensive methodology. The major advantage in using the kynurenine pathway as a screening tool is that the whole metabolic profile can be assessed concurrently on one machine.

Our research and development plan will involve (1) measuring the whole kynurenine pathway metabolic repertoire in brain cancer patient blood and correlating these levels with tumour progression and brain cancer subtype and; (2) assessing the effect of novel kynurenine pathway inhibitors on brain cancer cell growth using cells grown in the laboratory. If this approach is successful then our next step will be to move our work into preclinical models.

Impact

A clinically useful role of potential kynurenine pathway biomarkers would be to improve accuracy in the prediction of tumour grade and tumour progression. Treatment would be personalised to the exact tumour grade and subtype, which may significantly improve patient outcome. Further, our proposed research will advance the knowledge base of kynurenine pathway involvement in cancer pathology, which will promote new treatment options for patients.

Team & partners

Our research has enabled us to forge major collaborative opportunities with Macquarie University Hospital clinicians and researchers. We will also be working with clinicians at the Douglas Hanly Moir pathology laboratory. Dr Kerrie McDonald, leader of the Cure Brain Cancer Neuro-Oncology Group at the Lowy Cancer Research Centre, will also be working with us to advance this project.

Co-investigator: Prof Gilles Guillemin, Macquarie University, NSW

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